Vascular implants and methods of fabricating the same

ABSTRACT

The present invention is directed to vascular implants and methods for fabricating the same. The implantable devices include but are not limited to stents, grafts and stent grafts. In many embodiments, the devices include one or more side branch lumens interconnected with the main lumen.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.12/029,147 filed Feb. 11, 2008, which is a non-provisional of U.S.Provisional Patent Application No. 60/889,157, filed on Feb. 9, 2007,the content of which is incorporated herein by reference in itsentirety.

FIELD OF THE INVENTION

The present invention relates to the treatment of vascular disease,including for example aneurysms, ruptures, psuedoaneurysms, dissections,exclusion of vulnerable plaque and treatment of occlusive conditions,and more particularly, the invention is related to implantable devicesand methods for fabricating the same.

BACKGROUND OF THE INVENTION

It is well known in the prior art to treat vascular disease withimplantable stents and grafts. For example, it is well known in the artto interpose within a stenotic or occluded portion of an artery a stentcapable of self-expanding or being balloon-expandable. Similarly, it isalso well known in the prior art to use a graft or a stent graft torepair highly damaged or vulnerable portions of a vessel, particularlythe aorta, thereby ensuring blood flow and reducing the risk of ananeurysm or rupture.

A more challenging situation occurs when it is desirable to use a stent,a graft or a stent graft at or around the intersection between a majorartery (e.g., the abdominal aorta) and one or more intersecting arteries(e.g., the renal arteries). Use of single axial stents or grafts mayeffectively seal or block-off the blood flow to collateral organs suchas the kidneys. U.S. Pat. No. 6,030,414 addresses such a situation,disclosing use of a stent graft having lateral openings for alignmentwith collateral blood flow passages extending from the primary vesselinto which the stent graft is positioned. The lateral openings arepre-positioned within the stent based on identification of the relativepositioning of the lateral vessels with which they are to be aligned.U.S. Pat. No. 6,099,548 discloses a multi-branch graft and a system fordeploying it. Implantation of the graft is quite involved, requiring adiscrete, balloon-deployable stent for securing each side branch of thegraft within a designated branch artery. Additionally, a plurality ofstylets is necessary to deliver the graft, occupying space within thevasculature and thereby making the system less adaptable forimplantation into smaller vessels. Further, delivery of the graft andthe stents requires access and exposure to each of the branch vesselsinto which the graft is to be placed by way of a secondary arteriotomy.These techniques, while effective, may be cumbersome and somewhatdifficult to employ and execute, particularly where the implant siteinvolves two or more vessels intersecting the primary vessel, all ofwhich require engrafting.

The use of bifurcated stents for treating abdominal aortic aneurysms(AAA) is well known in the art. These stents have been developedspecifically to address the problems that arise in the treatment ofvascular defects and or disease at or near the site of a bifurcation.The bifurcated stent is typically configured in a “pant” design whichcomprises a tubular body or trunk and two tubular legs. Examples ofbifurcated stents are provided in U.S. Pat. Nos. 5,723,004 and5,755,735. Bifurcated stents may have either unitary configurations ormodular configurations in which the components of the stent areinterconnected in situ. In particular, one or both of the leg extensionsare attachable to a main tubular body. Although the delivery of modularsystems is less difficult due to the smaller sizes of the components, itis difficult to align and interconnect the legs with the body lumen withenough precision to avoid any leakage. On the other hand, while unitarystents reduce the probability of leakage, their larger structure isoften difficult to deliver to a treatment site having a constrainedgeometry.

While the conventional bifurcated stents have been used somewhatsuccessfully in treating AAA, they are not adaptable where the anatomyof the implant site is irregular, i.e., where the shape of the majorartery, generally or at or around the branch artery intersectionzone(s), is other than substantially straight, and/or where the anatomyof the implant is variable from patient to patient. The aortic arch isan example of the vascular anatomy that presents both of thesechallenges.

The highly curved anatomy of the aortic arch requires a stent that canaccommodate various radii of curvature. More particularly, the stentwall is required to be adaptable to the tighter radius of curvature ofthe underside of the aortic arch without kinking while being able toextend or stretch to accommodate the longer topside of the arch withoutstretching the stent cells/wire matrix beyond its elastic capabilities.

Additionally, the variability of the anatomy of the aortic arch fromperson to person makes it a difficult location in which to place a stentgraft. While the number of branch vessels originating from the arch ismost commonly three, namely, the left subclavian artery, the left commoncarotid artery and the innominate artery, in some patients the number ofbranch vessels may be one, more commonly two and in some cases four,five or even six. Moreover, the spacing and angular orientation betweenthe tributary vessels are variable from person to person.

Still yet, placing stents/grafts within the aortic arch presentsadditional challenges. The arch region of the aorta is subject to veryhigh blood flow and pressures which make it difficult to position astent graft without stopping the heart and placing the patient oncardiopulmonary bypass. Moreover, even if the stent graft is able to beproperly placed, it must be secured in a manner to endure the constanthigh blood flow, pressures, and shear forces it is subjected to overtime in order to prevent it from migrating or leaking. Additionally, theaorta undergoes relatively significant changes (of about 7%) in itsdiameter due to vasodilation and vasorestriction. As such, if an aorticarch graft is not able to expand and contract to accommodate suchchanges, there may be an insufficient seal between the graft and theaortic wall, subjecting it to a risk of migration and/or leakage.

In order to achieve alignment of a side branch stent or a lateralopening of the main stent with the opening of a branch vessel, a customstent, designed and manufactured according to each patient's uniquegeometrical constraints, would be required. The measurements required tocreate a custom-manufactured stem to fit the patient's unique vascularanatomy could be obtained using spiral tomography, computed tomography(CT), fluoroscopy, or other vascular imaging system. However, while suchmeasurements and the associated manufacture of such a custom stent couldbe accomplished, it would be time consuming and expensive. Furthermore,for those patients who require immediate intervention involving the useof a stent, such a customized stent is impractical. In these situationsit would be highly desirable to have a stent which is capable ofadjustability in situ while being placed and which can accommodatevariable anatomy once placed. It would likewise be highly desirable tohave the degree of adjustability sufficient to allow for a discretenumber of stents to be manufactured in advance and available toaccommodate the required range of sizes and configurations encountered.

Another disadvantage of conventional stents and stent grafts is thelimitations in adjusting the position of or subsequently retrieving thestent or stent-graft once it has been deployed. Often, while the stentis being deployed, the final location of the delivered stent isdetermined not to be optimal for achieving the desired therapeuticeffect. During deployment of self-expanding stents, the mode ofdeployment is either to push the stent out of a delivery catheter, ormore commonly to retract an outer sheath while holding the stent in afixed location relative to the vasculature. In either case the distalend of the stent is not attached to the catheter and, as such, is ableto freely expand to its maximum diameter and seal with the surroundingartery wall. While this self-expanding capability is advantageous indeploying the stent, it presents the user with a disadvantage whendesiring to remove or reposition the stent. Some designs utilize atrigger wire(s) to retain the distal end of the stent selectively untilsuch time as full deployment is desired and accomplished by releasingthe “trigger” wire or tether wire(s). The limitation of this design isthe lack of ability to reduce the diameter of the entire length ofstent. The significance of not being able to reduce the diameter of thestent while positioning it is that the blood flow is occluded by thefully expanded main body of the stent even though its distal end is heldfrom opening.

Another disadvantage of conventional stent-grafts is the temporarydisruption in blood flow through the vessel. In the case of balloondeployable stents and stent-grafts, expansion of the balloon itselfwhile deploying the stent or stent-graft causes disruption of blood flowthrough the vessel. Moreover, in certain applications, a separateballoon is used at a location distal to the distal end of the stentdelivery catheter to actively block blood flow while the stent is beingplaced. In the case of self-expanding stent-grafts, the misplacement ofa stent graft may be due to disruption of the arterial flow duringdeployment, requiring the placement of an additional stent-graft in anoverlapping fashion to complete the repair of the vessel. Even withoutdisruptions in flow, the strong momentum of the arterial blood flow cancause a partially opened stent-graft to be pushed downstream by thehigh-pressure pulsatile impact force of the blood entering the partiallydeployed stent graft.

With the limitations of current stent grafts, there is clearly a needfor improved stents and stent grafts for treating vascular disease andconditions affecting interconnecting vessels (i.e., vascular trees), andfor improved means and methods for implanting them which address thedrawbacks of the prior art.

SUMMARY OF THE INVENTION

The present invention is directed to vascular implants and methods forfabricating the same. The implantable devices generally include atubular member or lumen, most typically in the form of a stent, a graftor a stent graft, where the device may further include one or morebranching or transverse tubular members or lumens laterally extendingfrom the main or primary tubular member.

The implant sites addressable by the subject devices may be any tubularor hollow tissue lumen or organ; however, the most typical implant sitesare vascular structures, particularly the aorta. Thus, devices of theinvention are constructed such that they can address implant sitesinvolving two or more intersecting tubular structures and, as such, areparticularly suitable in the context of treating vascular trees such asthe aortic arch and the infrarenal aorta.

The devices and their lumens are formed by interconnected cells wherethe cells are defined by struts which are preferably made of an elasticor superelastic material such that changes and adjustments can be madeto various dimensions, orientations and shapes of the device lumens. Assuch, another feature of the present invention involves the reduction orexpansion of a dimension, e.g., diameter and length, of one or more thedevice lumens. Typically, a change in one dimension is dependent upon orresults in an opposite change in another dimension, i.e., when thediameter of the stent lumen is reduced, the length of the stentincreases, and visa versa. The material construct of the devices furtherenables the one or more side branch lumens of the devices to bepositioned at any appropriate location along the length of the mainlumen and at any angle with respect to the longitudinal axis of the mainlumen. Where there are two or more side branch lumens, the lumens may bespaced axially and circumferentially angled relative to each other toaccommodate the target vasculature into which the implant is to beplaced.

Still yet, the devices are constructed to have any suitable preformedshape, such as a curved tubular configuration, tapered or flared luminalends and reduced or expanded central portions. Alternatively, thedevices may have a naturally straight cylindrical configuration which issufficiently flexible, both axially and radially, to accommodate thevasculature within which it is implanted. On the other hand, certainportions of the devices may be selected to have greater stiffness. Assuch, another aspect of the invention is to incorporate selectiveflexibility/stiffness into the device upon fabrication, where the gauge,thickness or width of the materials forming the lumens can be variedover the entirety of the device.

The subject devices may further include other materials which form atleast a portion of the device, whether such portions may include thestent or the graft or all or portions of both. In certain embodiments,the graft is made from a biomaterial, such as an extracellular matrix,or other biodegradable material, which is coated or attached to at leasta portion of the stent, whereby the material facilitates cellularintegration of the device into the vessel wall.

The subject devices include additional features for improving andfacilitating their delivery, deployment, positioning, placement,securement, retention and/or integration within the vasculature, as wellas features which enable the devices to be removed or repositionedsubsequent to at least partial deployment within the body.

These and other objects, advantages, and features of the invention willbecome apparent to those persons skilled in the art upon reading thedetails of the invention as more fully described below.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention is best understood from the following detailed descriptionwhen read in conjunction with the accompanying drawings. It isemphasized that, according to common practice, the various features ofthe drawings are not to-scale. On the contrary, the dimensions of thevarious features are arbitrarily expanded or reduced for clarity. Alsofor purposes of clarity, certain features of the invention may not bedepicted in some of the drawings. Included in the drawings are thefollowing figures:

FIG. 1 illustrates an embodiment of a branched stent of the presentinvention in a natural, deployed state;

FIG. 2 illustrates another embodiment of a branched stent of the presentinvention in a natural, deployed state;

FIG. 3A illustrates another embodiment of a branched stent in which theside branch lumens are angled; FIG. 3B illustrates an end view of thestent of FIG. 3A;

FIG. 4 shows an embodiment of a branched stent fabricated from wirehaving more than one gauge;

FIG. 5 shows another embodiment of a branched stent fabricated from wirehaving more than one gauge;

FIG. 6 illustrates an enlargement of a portion of a stent bodyfabricated from wire having more than one gauge;

FIGS. 7A-7C illustrate various exemplary mandrel designs for fabricatingthe stents and stent grafts of the present invention;

FIG. 8 illustrates one manner in grafting a stent of the presentinvention;

FIG. 9 illustrates another embodiment of an implant of the presentinvention having a cardiac valve operatively coupled to it;

FIGS. 10A and 10B are schematic illustrations of single stent cells;

FIGS. 11A-11G illustrate various steps in a method of fabricating agraft covering for a stent grafts of the present invention;

FIG. 12A illustrates a mandrel apparatus for forming convolutions in thegraft covering of FIGS. 11A-11F; FIG. 12B is an enlarged cut-out view ofa portion of the mandrel apparatus of FIG. 12A;

FIGS. 13A-13C illustrate various steps in another method of fabricatinga graft covering for a stent grafts of the present invention; and

FIG. 14 illustrates another mandrel apparatus of the present inventionfor forming the convolution pattern in the graft of FIG. 13D.

DETAILED DESCRIPTION OF THE INVENTION

Before the devices, systems and methods of the present invention aredescribed, it is to be understood that this invention is not limited toparticular therapeutic applications and implant sites described, as suchmay vary. It is also to be understood that the terminology used hereinis for the purpose of describing particular embodiments only, and is notintended to be limiting, since the scope of the present invention willbe limited only by the appended claims.

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this invention belongs. The term “implant” or“implantable device” as used herein includes but is not limited to adevice comprising a stent, a graft, a stent-graft or the like. The terms“proximal” and “distal” when used with reference to the implantabledevices of the present invention, these terms are to be understood toindicate positions or locations relative to the intended implant sitewhen it is operatively positioned therein. As such, proximal refers to aposition or location closer to the origin or upstream side of bloodflow, i.e., the closer to the heart, the more proximal the position.Likewise, distal refers to a position or location further away from theorigin or closer to the downstream side of blood flow.

Referring now to the figures, the present invention will now bedescribed in greater detail. It is noted that while each of theillustrated devices has a primary or main tubular member and at leastone laterally extending tubular branch, the implantable devices of thepresent invention need not have side branches.

FIG. 1 illustrates one variation of an implantable device 2 having aprimary tubular portion, body or member 4 and laterally extending sidebranches 6 a, 6 b and 6 c, interconnected and in fluid communicationwith main body 4 by way of lateral openings within the body. Theproximal and distal ends of the main tubular member 4 terminate incrowns or apexes 8, the number of which may vary. The distal ends of theside branches 6 a, 6 b and 6 c terminate in crowns or apexes 10 a, 10 band 10 c, respectively, the number of which may also vary. Device 2 isparticularly configured for implantation in the aortic arch whereprimary tubular member 4 is positionable within the arch walls andtubular branches 6 a, 6 b and 6 c are positionable within the innominateartery, the left common carotid artery and the left subclavian artery,respectively.

FIG. 2 illustrates another variation of a device 12 having a primarytubular portion or member 14 and laterally extending branches 16 a and16 b, interconnected and in fluid communication with main body 14 by wayof lateral openings within the body. The proximal and distal ends of themain tubular member 14 terminate in crowns or apexes 18 which areemployed as described above with respect to FIG. 1 while the distal endsof the side branches 16 a and 16 b terminate in crowns or apexes 18 aand 18 b, respectively. Device 12 is particularly configured forimplantation in the infra-renal aorta where primary tubular member 14 ispositionable within the walls of the aorta and tubular branches 16 a and16 b are positioned within the right and left renal arteries,respectively.

The subject devices are fabricated at least in part from one or morestruts 5 which form interconnected cells 15. This construct enables thedevices to be selectively manipulated to adjust at least a dimension(diameter and/or length), shape or orientation of the device. By“manipulated,” it is meant that the device can be constrained,compressed, expanded, stretched, twisted, angled, etc. Whether any ofthese manipulations are necessary is at least partially dependent on theneutral or natural size of the stent lumens, the size of the vesselsinto which the lumens are to be implanted, the cross-sectional profileof the delivery system through which they are delivered to the implantsite and the anatomy or spatial/dimensional configuration of the vesselinto which the implant is to be positioned. For most endovascularapplications, the lumenal diameters require reduction in order to fitwithin a delivery system, and then require subsequent reversal of thereduction to properly engage the vessel into which they are deployed.However, the lumen diameters, once deployed within the vasculature, maynot necessarily fully expand to their natural/neutral size as they willbe constrained by the vasculature. In some instances, the stent lumensmay require expansion subsequent to deployment within the vasculature inorder to adequately engage the vessel walls.

Generally, the devices of the present invention have a first, unreducedor neutral dimension “X” and a second or reduced dimension “Y” which isanywhere from one half or less to one tenth or less of the firstdimension “X.” Such a dimension is often a diameter or length of thedevice where the diameter or length of at least the main lumen of thestent, and most typically of all of the side branch lumens as well, canbe changed or moderated between X and Y.

Typically, the subject devices for most vascular applications will havea main branch lumen having an unconstrained length in the range fromabout 1 cm to about 25 cm and an unconstrained diameter in the rangefrom about 2 mm to about 42 mm; and side branch lumens having anunconstrained length in the range from about 0.5 cm to about 8 cm and anunconstrained diameter in the range from about 2 mm to about 14 mm. Foraortic applications, the unconstrained length of the main lumen istypically from about 8 cm to about 25 cm and the unconstrained diameteris in the range from about 15 mm to about 42 mm; and the side branchlumens will have an unconstrained length in the range from about 2 cm toabout 8 cm and an unconstrained diameter in the range from about 5 mm toabout 14 mm. Where the dimension is the diameter of the main lumen ofthe stent, the reduced diameter is more likely to be closer to one tenthof the unreduced diameter. For renal applications, the main branch lumenwill have an unconstrained length in the range from about 2 cm to about20 cm and an unconstrained diameter in the range from about 12 mm toabout 25 mm; and the side branch lumens will have an unconstrainedlength in the range from about 0.5 cm to about 5 cm and an unconstraineddiameter in the range from about 4 mm to about 12 mm. For coronaryapplications, the main branch lumen will have an unconstrained length inthe range from about 1 cm to about 3 cm and an unconstrained diameterfrom about 2 mm to about 5 mm; and the side branch lumens will have anunconstrained length in the range from about 0.5 cm to about 3 cm and anunconstrained diameter in the range from about 2 mm to about 5 mm. Forapplications in smaller vessels, such as the neurovasculature, thesedimensions will of course be smaller. In certain applications,particularly where treating a vascular aneurysm having a relativelylarge neck section located near a juncture between the main vessel and atributary vessel, it may be preferential to provide a branched stentwhere the side branch lumens are relatively longer than average. Thelengthier stent branches can bridge the neck opening while maintainingsufficient length at their distal ends to extend a distance into avascular side branch sufficient to anchor the stent.

Adjustability in the length and/or diameter of the main lumen as well asthe length and/or diameter of the side branch lumens of the devicesenables them to accommodate curvaceous or tortuous vasculatureencountered along the delivery path and at the implant site. In oneaspect, the diameters of the device lumens may be compressed to enablethe device to fit within a smaller-diameter delivery sheath or catheter,yet they may also be expandable beyond a natural or neutral diameter toengage the vasculature wall at the implant site. In many embodiments,changing the diameter or length of a lumen results in a correspondingchange in the other dimension. More specifically, compressing a lumen'sdiameter will increase its length, and expanding a lumen's diameter mayresult in foreshortening of the lumen's length.

In another aspect, the orientation of a side branch with respect to themain branch may be adjustable within a certain range. In particular, theside branches are rotationally adjustable relative to the main lumen,i.e., the angle at which each of the side branches intersects the mainlumen may be varied. FIG. 3A illustrates an implant device 20 in whichside branch lumens 24 and 26 each has an angular orientation, defined byangle α, with respect to main lumen 22, and has an angular orientation,defined by angle β, with respect to each other. FIG. 3B is an end viewof implant device 20 which illustrates the circumferential orientation,defined by angle θ, between side branch lumens 22 and 24. Typical rangesof the various angles are as follows: from about 100 to about 170° forangle α, from 0° to about 170° for angle β, and from 0° to 360° forangle θ.

Each of a stent's branched lumens has a naturally biased orientation inan unconstrained, pre-deployed condition, i.e., the neutral state. Thisorientation range is built into the device upon fabrication and isselected to accommodate any possible variation in the anatomy beingtreated. One or more of the branched lumens may be selectively adjustedwithin the orientation range upon delivery and placement of the branchlumens within the respective vessel lumens. For example, the stent maybe fabricated with one or more side branches having neutral orientationsat substantially right-angles with respect to axis of the main lumen,which natural orientation may be adjusted in any direction toaccommodate the orientation of side branch vessel at the implant siteinto which the stent is placed. Such angular orientation of the sidebranch lumens with respect to the main lumen may be axial,circumferential or both. Where two or more side branches are employed ona subject device, the linear distance between the side branches may alsobe varied by selective stretching or foreshortening of the stentmaterial positioned between the side branches. In this way, the subjectinvention is able to address patient-to-patient anatomicalinconsistencies with only a single-sized device. In one application, thedevices are constructed to accommodate the variability in spacingbetween or the angular orientation of the tributary vessels of theaortic arch.

The shape of the implant's lumens may also vary or be adjusted as neededto accommodate the vessel into which it is positioned. Each of adevice's lumens may have a natural, preformed shaped, e.g., curved, thataccommodates the shape of the vessel into which it is to be placed.Alternatively, the lumens may be made with a neutrally straightconfiguration but are flexible enough to accommodate the naturalcurvature of the vessel into which they are implanted.

The subject devices may also be fabricated such that their lumens mayhave constant or variable stiffness/flexibility along their lengths aswell as about their circumferences. Greater flexibility can betteraccommodate curvaceous vasculature encountered during delivery and atthe implant site. Such a feature is highly beneficial in aortic archstenting applications due to the relatively “tight” curve of the arch.Enhanced stiffness, on the other hand, particularly at the end portionsof a lumen, imparts a greater radial force thereby resisting migrationof the device within the vasculature after placement. Variableflexibility/stiffness may be implemented in a variety of ways.

The gauge or thickness of the strut or struts (i.e., the elementalportions that form a stent cell) used to fabricate the devices may varywhere thicker gauges impart greater stiffness and thinner gauges impartgreater flexibility. The struts of a stent may vary in diameter (in wireembodiments) or thickness or width (in sheet and cut tube embodiments).In one variation, a single wire or filament may be used where the gaugeselectively varies along its length. The thicker gauge portions are usedto form at least the end portions of the stent lumen(s) to increasetheir radial force thereby reducing the risk of stent migration.Conversely, the narrower gauge portion(s) of the wire form at least acentral portion of the main stent lumen (and may also form portions ofthe side branch lumens) which may be relatively more flexible than theend portions to facilitate delivery of the stent within tortuous orcurving vasculature or enabling the device to be compact into thedelivery sheath more easily.

In other embodiments, more than one wire is used where the wires eachhave constant gauges along their respective lengths but differ from wireto wire. Larger gauge wire(s) may be used to form the stent ends orother areas where increased stiffness is required while narrower gaugewire(s) may be used to form other portions, e.g., the central portionsof the stent lumens, where increased flexibility is required or thecells of the side branch stents where decreased radial force is requiredrelative to the radial force required for the main body portion.Additionally or alternatively, the larger gauge wire can be selectivelydoubled-over or wrapped with the narrow gauge wire at selected points orlocations about the stent to bolster the stiffness at those particularsites.

In one variation, two or more wires may be employed to form the devicewhereby the wire ends, i.e., four wire ends in the case of a device madefrom two wires, are joined together. The location(s) about the lumens atwhich the wires cross—each and/or at which their ends are joined aboutis/are selected to minimize stiffness in certain areas along or aboutthe lumen and/or to enhance stiffness in one or more other areas of thedevice, i.e., to provide relative stiffness and flexibility betweenportions of the stent. For example, in aortic arch applications, theportion of the main lumen of the stent intended to be aligned along theinferior wall of the arch is preferentially relatively more flexibleand/or less stiff than the portion of the stem intended to be alignedalong the superior wall of the arch, as the inferior wall has a tighterradius of curvature. Accordingly, it may be desirable to minimize thejoinder and/or intersection points of the wires along this portion ofthe stent.

FIGS. 4-6 illustrate embodiments of the subject devices which employvarying gauges of wire. The main tube 32 of device 30 of FIG. 4 isfabricated from at least two gauges of wire (either one wire having atleast two gauges or two or more wires having different gauges) where aheavier gauge 36 is used to fabricate end portions 34 a and 34 b and athinner gauge 42 is used to fabricate other portions 44 therebetween. Athicker gauge wire 36 is also selectively weaved or threaded throughoutmain tube 32. For example, wire(s) 36 is/are used at the junctures 40 a,40 b, 40 c between the side branch lumens 46 and main lumen 32. Whileproviding stability at the junctures, the heavier gauge wire does notimpede a side branch stent's flexibility to fold against the main lumenfor purposes of delivery through a sheath. Additionally, the thickerwire 36 may be crossed-over on itself or, where two or more wires areused, the wires may be caused to intersect at other locations 38 a, 38 bwhere additional stiffness is desired. Here, the portions of the mainstent lumen directly between (and on the same side as) the side branchlumens 40 a, 40 b, 40 c are free of the thicker gauge wire. Minimizingthe wire gauge at these locations increases flexibility and the abilityto adjust (stretch or compress) the linear distance between the sidebranches, a feature quite often needed for aortic arch applications

Main lumen 52 of device 50 of FIG. 5 is fabricated in a similar mannerwith end portions 54 a, 54 b having a thicker gauge wire 56 and morecentrally located portions 60 having a narrow gauge wire 62. Unlikedevice 30, the junctures between the side branch lumens 64 and the mainlumen 52 are not reinforced with the thicker gauge wire. Here, also,both sides of main lumen 52 are somewhat equally reinforced (atlocations 58 a-58 e) to impart substantially equal flexibility/stiffnesson both sides of the device 50.

FIG. 6 shows an enlarged portion 70 of a device of the present inventionfabricated from two wires, one having a thinner gauge 72 and the otherhaving a thicker gauge 74. The thinner gauge wire 72 is used tofabricate the majority of the stent body which is reinforced in certainareas by the thicker gauge wire 74. As mentioned above, thereinforcement can be accomplished by weaving together two or morelengths of the thinner gauge wire 72 and/or by weaving the thicker gaugewire 74 along a weave pattern or line of thinner gauge wire, asreferenced by 76 in the figure. Alternatively or additionally, the wiresmay be intersected at certain selected points 78 about the area of thestent body to increase stiffness at those points.

The devices of the present invention are additionally advantageous inthat they are self-securing to prevent migration within the vasculature.Such a feature may be implemented in a variety of different ways. First,the device lumens may be constructed having ends (for both main and sidebranches) which have expanded or flared diameters that place sufficientradial force on the interior wall of the vessel into which they areimplanted to resist against intravascular pressures. As mentioned above,thicker gauge wire at the end portions of the device may provideadditional radial force. Additionally or alternatively, the number ofapices at the stent ends may be increased as needed to increase theradial force at the end portions. Typically, at least three apices areemployed at each of the lumenal ends (main lumen and side branchlumens), where larger lumens require more apices to maintain the desireradially force to be placed on the vessel wall. In branched devices,migration prevention may be addressed by integrating the cells of a sidebranch lumen with the cells of the main body lumen. More specifically,the interconnection of the side branch lumen to the main body lumen isaccomplished by forming the side branch lumen and the main body lumenfrom the same wire or filament. Thus, when the side branch is deployedwithin and held in place by the side branch artery, the main body of thestent cannot migrate. Such “passive” anchoring mechanisms areatraumatic, as opposed to an active anchoring means, such as barbs orhooks, which may damage the cellular structures of the implant siteleading to smooth muscle proliferation, restenosis, and other vascularcomplications such as perforations, tearing or erosion.

As mentioned above, the implantable devices of the present invention mayinclude a stent or a graft or a combination of the two, referred to as astent graft, a stented graft or a grafted stent. The stents and graftsof the present invention may be made of any suitable materials known inthe art. Preferably, the stent cell structure is constructed of wire,although any suitable material may be substituted. The wire stent shouldbe elastically compliant, for example, the stent may be made ofstainless steel, elgiloy, tungsten, platinum or NITINOL but any othersuitable materials may be used instead of or in addition to thesecommonly used materials. The entire stent structure may be fabricatedfrom one or more wires woven into a pattern of interconnected cellsforming, for example, the closed chain link configuration illustrated inFIG. 6.

The stent structure may have asymmetrical cell sizes, e.g., cell sizemay vary along the length or about the circumference of the stent. Forexample, in one variation, as illustrated in FIGS. 10A and 10B, asubject stent has a first or larger cell size 82 at one or more sectionsof its lengths and has a second or smaller cell size 84 at one or moreother sections of its length. Here “cell size” is referring to thedimension of the cell along the longitudinal direction 86 of the stent.The smaller or narrow cells 84 provide greater radial force to the stentas well as better conformability to curved vascular geometry. As such,the length portions at the ends of the main stent lumen and at selectedcentral portions of the main lumen that may be subject to particularlycurved vasculature. For example, in aortic arch applications, smallercell sizes at the length portion(s) extending between the side branchstent lumens may be beneficial as the portions, after implantation ofthe stent, are positioned at the apex of the curve or at the sharpestcurvature of the arch, particularly at the inside curve (lower archcurve). With smaller cells, the likelihood of the cell struts extendinginto the stent lumen is minimized. In other stent variations, the cellsize of the side branch lumens is gradually reduced in the distaldirection. This facilitates the ability to selectively stretch thedistal most portion of the side branch lumens and, thus, makes it easierfor a physician to guide the distal end of the side branch into adesignated vessel.

The wire-formed stents of the present invention may be fabricated inmany ways. One method of making the wire stent is by use of a mandreldevice such as the mandrel devices 90, 100 and 110 illustrated in FIGS.7A-7C, respectively. Each of the devices has at least a main mandrelcomponent 92, 102, and 112, respectively, with a plurality ofselectively positioned pinholes 94, 104 and 114, respectively, withinwhich a plurality of pins (not shown) are selectively positioned, orfrom which a plurality of pins is caused to extend. As is described inmore detail below, the stent structure is formed by selectively wrappinga wire around the pins. Where the stent is to have one or more sidebranch lumens, the mandrel device, such as device 110 of FIG. 7C, may beprovided with at least one side mandrel 116 extending substantiallytransverse to the main mandrel 112, where the number of side mandrelspreferably corresponds to the number of stent side branches to beformed. The mandrel devices may be modular where side branch mandrels ofvarying diameters and lengths can be detachably assembled to the mainmandrel. The configuration of the main mandrel as well as the sidebranch mandrel(s) may have any suitable shape, size, length, diameter,etc. to form the desired stent configuration. Commonly, the mandrelcomponents have a straight cylindrical configuration (see FIGS. 7A and7C) having a uniform cross-section, but may be conical with varyingdiameters along a length dimension (see FIG. 7B), frustum conical, havean oval cross-section, a curved shape, etc.

The pins may be retractable within the mandrel components or arethemselves removable from and selectively positionable within holesformed in the mandrel components. Still yet, the mandrel device may beconfigured to selectively extend and retract the pins. The number ofpins and the distance and spacing between them may be varied to providea customized pin configuration. This customization enables thefabrication of stents having varying sizes, lengths, cell sizes, etc.using a limited number of mandrel components. For example, in onevariation, the pins are arranged about the mandrel components in analternating pattern such as for example, where about 50% of the pinholesper row will be filled with pins. Alternatively, a selection of mandrelsmay be provided, each having a unique pinhole pattern which in turndefines a unique stent cell pattern.

To form the stent, a shape memory wire, such as a NITINOL wire, having aselected length and diameter are provided. Typically, the length of thewire ranges from about 1 foot (in the case of a short “cuff” extender)to about 12 feet long, but may be longer if needed or shorter if morepractical, depending on the desired length and diameter of the stent tobe formed. The wire's diameter is typically in the range from about0.001 to about 0.020 inch. After providing a mandrel device havingwinding pins at the desired points or locations on the mandrelcomponents, the wire is wound about the pins in a selected direction andin a selected over-and-under lapping pattern, e.g., a zigzag pattern, toform a series of interconnected undulated rings resulting in a desiredcell pattern.

An exemplary wire winding pattern is illustrated in FIG. 6. Startingfrom one end of the main mandrel, the wire 72 is wound around the pins80 in a zigzag pattern back and forth from one end of the main mandrelto the other until the cells of the main lumen of the stent have beenformed. Next, the same or a different wire is used to form the sidebranch lumen(s) where the wire is wrapped in a zigzag fashion from thebase of the side branch mandrel to the distally extending end and backagain until all of the cells of the side branch have been created. Thenthe wire is wound about the main mandrel along a path that is at anangle to longitudinal axis of the main mandrel where the wire is doubledover itself along certain cell segments, as indicated by referencenumber 76. It should be noted that any lumen of the stent may befabricated first, followed by the others, or the winding pattern may besuch that portions of the various lumens are formed intermittently.

The mandrel device with the formed wire stent pattern are then heated toa temperature in the range from about 480° C. to about 520° C. andtypically to about 490° C. for approximately 20 minutes in a gaseousenvironment, however, this time may be reduced by using a salt bath. Theduration of the heat-setting step is dependent upon the time necessaryto shift the wire material from a Martensitic to an Austenitic phase.The assembly is then air cooled or placed into a liquid quench bath(which can be water or other suitable liquid) for 30 seconds or more andthen allowed to air dry. Once the stent is sufficiently dried, the pinsare either pulled from the mandrel device or retracted into the hollowcenter of the mandrel by an actuation of an inner piece which projectsthe pins out their respective holes in the outer surface of the mandrel.Once the side branch mandrels are removed, the stent, with itsinterconnected lumens, can then be removed from the mandrel device.Alternatively, with the mandrel components detached from one another,one of the lumens, e.g., the main stent lumen, may be formed firstfollowed by formation of a side branch lumen by attachment of a sidemandrel to the main mandrel.

As discussed above, selected regions of the stent may be fabricated fromwire selectively reduced in diameter. The selective diameter reductionmay be accomplished by selectively etching or e-polishing the certainstent struts located at the portions of the stent where less stiffnessand a reduced radial force are desired. This can be done by selectiveimmersion of the side branch in an acid during manufacture to reduce theamount of metal in a particular region of the stent. Another method toaccomplish the desired result of preferentially reducing side branchlongitudinal stiffness and/or outward radial force of the side branchcomponent is to use an electropolishing apparatus. By placing the wovensolid wire stent into an electrolyte bath and applying a voltagepotential across an anode-cathode gap, where the stent itself is theanode, metal ions are dissolved into the electrolytic solution.Alternatively, or subsequently, the process may be reversed wherein thestent becomes the cathode and the side branch or other selected regionof the stent may be electroplated with a similar or different metal inionic solution, for instance gold or platinum, in order to either changethe mechanical properties or to enhance the radiopacity of the selectedregion. Those skilled in the art of electroplating and electropolishingwill recognize that there are techniques using a “strike” layer of asimilar material to the substrate in order to enhance the bonding of adissimilar material to the substrate. An example would be the use of apure nickel strike layer on top of a NITINOL substrate in order tosubsequently bond a gold or platinum coating to the substrate.

Another method of making the stent is to cut a thin-walled tubularmember from a tube or flat sheet of material by removing portions of thetubing or sheet in the desired pattern for the stent, leaving relativelyuntouched the portions of the metallic tubing which are to form thestent. The sheet material may be made of stainless steel or other metalalloys such as tantalum, nickel-titanium, cobalt-chromium, titanium,shape memory and superelastic alloys, and the noble metals such as goldor platinum.

In addition to these methods, other techniques known to one of skill inthe art may be employed to make the subject stents. Some of thesemethods include laser cutting, chemical etching, electric dischargemachining, etc.

Referring now to FIG. 8, where a stent graft 120 is to be formed by theaddition of a graft material 122, such as an ECM material, to thesubject stent 124, any manner of attaching the graft material to thewire form may be used. In one variation, the graft material is attachedby way of a suture 126. As such, one edge 128 of the graft material isstitched lengthwise to the stent frame 124 along the stents length,where at least one knot 130 is tied at each apex of the stent to securean end of the graft to the stent. Then the graft material 122 isstretched around the surface of the stent and the opposite edge 132 ofthe graft is overlapped with the already attached edge 128 andindependently stitched to the stent frame to provide a leak free surfaceagainst which blood cannot escape. The graft material is stretched to anextent to match the compliance of the stent so that it does not drapewhen the stent is in the expanded state. Upon complete attachment of thegraft material to the stent, the graft is dehydrated so that it snugglyshrinks onto the stent frame similar to heat shrink tubing would whenheated.

FIGS. 11A-11F illustrate a method of fabricating a stent graft of thepresent invention from a woven or knitted-type graft fabric, such aspolyester. As shown in FIG. 11A, a sheet 150 of the material or fabricis provided and preferably stretched in a direction 158 a, 158 bdiagonal to the natural weave 152 of the material (shown boldly and inexaggerated size in FIG. 1A for illustration purposes only). While thesheet is stretched, pieces or swatches of the material are cut from thesheet where the swatches have length and width dimensions correspondingto the length and circumference dimensions of the main lumen 154 andside branch lumens 156 of the stent graft to be formed. As illustratedin FIG. 11A, the material is preferably cut at an angle or diagonal tothe weave pattern 152 the swatches that forms the material. The stretchundergone by the material remains fixed with the resulting orientationof the pre-stretched weave pattern enabling the resulting grafts to behighly stretchable when stretched along an axis perpendicular (oropposite) to the direction of pre-stretch undergone by the material.Next, each of the side branch swatches 156 is folded to coapt opposingside edges of the material (not shown) which are then sutured togetherto form a side branch graft, as shown in FIG. 11B. The sutures may beformed in a “Z” stitch pattern 160 (commonly known to those skilled inart) to further enhance the stretchability of the juncture between thepieces of fabricated. The suture material may be made of radiopaquematerial for imaging the stent graft during the implantation procedure.As shown in FIG. 11C, holes 162 are cut or punctured into the main lumenswatch 154 corresponding to the number and location of the side branchstent graft lumens 156. The edges of the holes may be fused or otherwisetreated to prevent fraying of the material. As shown in FIG. 11D, theside branch grafts 156 are then sutured to swatch 154 at holes 162 usingthe same “Z” stitch pattern 164. Swatch 154 is then folded to coapt itslongitudinal edges 158 which are sutured together using the same stitchpattern 166 to form the main lumen graft. It may be particularlybeneficial to employ a radiopaque suture for stitching 166 to define alongitudinal marking on the stent graft for facilitating properalignment of the stent graft at a vascular implant site. Thecollectively assembled and attached fabric lumens form a branched graft170 (FIG. 11E) for covering a branched stent of the present invention.

While the pre-stretched graft lumens provide suitable stretchability forcovering a stent and also enhance the flexibility and adjustability ofthe resulting stent graft, as described above, “convoluting” the graftlumens may provide even further enhancement of these features. By“convoluting”, it is meant that preformed ridges and grooves are formedwithin the graft material about the graft's circumference (FIG. 11F),i.e., a wave pattern 175 a is formed along the graft's length, as bestillustrated by the schematic cross-sectional cut-out view in FIG. 11G.The convolutions may be formed in the graft material either prior toafter forming the graft's tubular lumens. A technique for forming theconvolutions subsequent to forming the tubular structures is describedbelow, however, those skilled in the art will appreciate and understandthat such convolutions may be formed while the graft material is stillin the planar form.

FIG. 12A illustrates a mandrel device 180 which may be used to form theconvolutions within the graft material, however, any suitable means andmethod may be employed. Mandrel apparatus 180 has a main mandrel 182sized for insertion within main lumen 154 of graft 170 and includes anynumber of secondary mandrel components 184 size for insertion into therespective side branch graft lumens 156. A plurality of threaded boreholes 192 extend radially within main mandrel 182 for receiving andsecuring to the distal threaded ends 190 of the respective side orsecondary mandrels 184. The selection of space apart bore holes 192allows mandrel device 180 to be used to convolute grafts having anynumber and spacing of side grafts. While not illustrated, bore holes maybe provided laterally of each other and/or on opposing sides of mainmandrel 180 to accommodate any configuration of stent, such as thoseillustrated in FIGS. 1, 2 and 3. The surface of each mandrel componenthas one or more sections 186, 188 within which a convolution pattern 175b has been formed. While the convolution pattern 175 b, best illustratedby the schematic cross-sectional cut-out in FIG. 12B, is shown having asquare wave pattern, any repetitive pattern (e.g., sine wave) may beemployed.

Fabricating the convolutions within graft 170 involves first insertingmain mandrel component 182 within graft 170 and positioning the graftover the mandrel's convolutions 175 b. Threaded bore holes 192 withinthe surface of mandrel 182 are then aligned with side branch lumens 156of graft 170 to allow for axial passage of the distal ends 190 of sidemandrels 184 through the side branch lumens 156 into bore holes 192. Thegraft material is then heat-set over mandrel device 180 whereby thefabric is caused to shrink and tighten around convolution pattern 175 b.Heat setting may be accomplished by placing the mandrel fitted with thegraft into an oven or by using a heat-emitting device where theheat-setting can be focused and targeted. The heat-setting causes theconvolution pattern 175 a to be formed within graft 170, as illustratedin FIGS. 11F and 11G. Once the pattern is set, the mandrels 182, 184 areremoved from the graft lumens. It is noted that the convolutions may beformed in each of the main graft and side branch grafts prior toattaching the grafts to each other by using each of the aforementionedmandrel components individually.

Optionally, another radiopaque stitching pattern 176 (shown in FIG. 11F)may be made within graft 170, running longitudinally along the mainlumen 154 and positioned approximately 180° about the circumference fromstitching pattern 166. The additional stitching pattern furtherfacilitates image-guided delivery and proper alignment of the stentgraft at an implant site. One or more corresponding radiopaque markingsmay also be provided within the stent delivery sheath whereby theradiopaque markings on the stent graft are aligned with those on thedelivery sheath to ensure proper orientation of the stent graft withinthe sheath, as well as to facilitate proper alignment of the deliverysheath during the implant procedure.

Referring now to FIGS. 13A-13D, another graft fabrication method isdescribed. Using the stretching and cutting techniques described abovewith respect to FIG. 11A, a single swatch 180 is formed having a crosspattern or the like whereby an elongated rectangular section 182 definesthe main graft lumen to be formed and one or more smaller and shorterrectangular sections 184, 186 intersecting main section 182 define theside branch graft lumens to be formed. Swatch 180 is then foldedlengthwise along section 182 such that the opposite edges of thematerial are apposed with each other. The apposed edges are thensutured, such as with the previously-described “Z” stitch pattern 190,to form the respective tubular structures 182, 184, 186 of a stent graft188, as shown in FIG. 11B. Unlike the graft embodiment of FIGS. 11A-11F,the stitching pattern that transforms the planar swatch to a tubularstructure is located on the side branch side, i.e., the “top”, of themain graft lumen 182, and extends along the lengths on both sides of theside branch lumens 184, 186.

Once the graft structure 188 is provided, convolutions 190 may then beformed in the graft material as substantially described above withrespect to FIG. 11F, but with a slight variation in order to preservethe diameter at the base of each of the side branch lumens 184.Specifically, as illustrated in FIG. 14, the mandrel device 194 used hasvoids 200 in the convolution pattern 196 about each of the threaded boreholes 198 for receiving the side branch lumen mandrels (not shown). Assuch, the resulting convolution pattern formed within the graft material182 provides corresponding areas 202 about the perimeter of the base ofeach of the side branch lumens 184, 186 which are devoid ofconvolutions. Forming convolutions, i.e., pleating the material, atthese base areas would otherwise reduce the overall perimeter, and thusthe diameter, of the side branch lumens. As previously discussed, anadditional yet optional radiopaque stitching pattern 192 may be placedwithin graft 188, running longitudinally along the main lumen 182 andpositioned approximately 180° about the circumference from stitchingpattern 190. As such both the “top” and “bottom” sides of graft 188 areprovided with a radiopaque marking to facilitate alignment of the graftwithin the delivery sheath as well as within the vasculature.

Upon final preparation of the graft by any method, the graft is engagedand affixed to the stent (not shown) to form the combined stent graft.The graft material may be positioned on either the outer or innersurface of the stent, or two graft layers may be used to encase thestent structure in between. For stent grafts in which the graft isexternal to the stent, the combined structure is formed by stretchingthe stent along its length and, while in the stretched condition,inserted it into one end of the main lumen of the graft. The stent ispulled there through and its side branches are aligned with thecorresponding side branch lumens of the graft which and positionedtherein. Once properly aligned, the stent is released from its stretchedcondition and allowed to expand into the graft to form a snug fitbetween the two. For stent grafts in which the graft is internal to thestent structure, graft is folded or otherwise compressed and drawingthrough the main lumen of the stent. The position of the graft isadjusted to align the side branch lumens of the graft with thecorresponding side branch lumens of the stent, and then the side lumensof the graft are pulled or pushed through the side lumens of the stent.

Each of these variations has its advantages. Specifically, with thegraft external to the stent, the graft material ensures apposition andsealing between the stent graft and the vessel wall, thereby minimizingthe risk of endoleak. Having the graft internal to the stent ensures anon-thrombogenic blood flow pathway through the stent graft. A stentgraft employing both an inner and outer graft covering clearly providesadvantages of both embodiments, however, with a potential increase inthe bulkiness of the device that may require larger delivery system.

The stent may be further anchored to the graft by a coating or bymechanical means, for example, by screws, cements, fasteners, sutures orstaples or by friction. Further, mechanical attachment means may beemployed to effect attachment to the implant site by including in thedesign of the stent a means for fastening it into the surroundingtissue. For example, the device may include metallic spikes, anchors,hooks, barbs, pins, clamps, or a flange or lip to hold the stent inplace.

The graft portion of a stent graft may be made from a textile, polymer,latex, silicone latex, polyetraflouroethylene, polyethylene, Dacronpolyesters, polyurethane silicon polyurethane copolymers or other orsuitable material such as biological tissue. The graft material must beflexible and durable in order to withstand the effects of installationand usage. One of skill in the art would realize that grafts of thesubject invention may be formulated by many different well known methodssuch as for example, by weaving or formed by dipping a substrate in thedesired material.

Biological tissues that may be used to form the graft material (as wellas the stent) include, but are not limited to, extracellular matrices(ECMs), acellularized uterine wall, decellularized sinus cavity liner ormembrane, acellular ureture membrane, umbilical cord tissue,decelluarized pericardium and collagen. Suitable ECM materials arederived from mammalian hosts sources and include but are not limited tosmall intestine submucosa, liver basement membrane, urinary bladdersubmucosa, stomach submucosa, the dermis, etc. Extracellular matricessuitable for use with the present invention include mammalian smallintestine submucosa (SIS), stomach submucosa, urinary bladder submucosa(UBS), dermis, or liver basement membranes derived from sheep, bovine,porcine or any suitable mammal.

Submucosal tissues (ECMs) of warm-blooded vertebrates are useful intissue grafting materials. Submucosal tissue graft compositions derivedfrom small intestine have been described in U.S. Pat. No. 4,902,508(hereinafter the '508 patent) and U.S. Pat. No. 4,956,178 (hereinafterthe '178 patent), and submucosal tissue graft compositions derived fromurinary bladder have been described in U.S. Pat. No. 5,554,389(hereinafter the '389 patent). All of these (ECMs) compositions aregenerally comprised of the same tissue layers and are prepared by thesame method, the difference being that the starting material is smallintestine on the one hand and urinary bladder on the other. Theprocedure detailed in the '508 patent, incorporated by reference in the'389 patent and the procedure detailed in the '178 patent, includesmechanical abrading steps to remove the inner layers of the tissue,including at least the lumenal portion of the tunica mucosa of theintestine or bladder, i.e., the lamina epithelialis mucosa (epithelium)and lamina propria, as detailed in the '178 patent. Abrasion, peeling,or scraping the mucosa delaminates the epithelial cells and theirassociated basement membrane, and most of the lamina propria, at leastto the level of a layer of organized dense connective tissue, thestratum compactum. Thus, the tissue graft material (ECMs) previouslyrecognized as soft tissue replacement material is devoid of epithelialbasement membrane and consists of the submucosa and stratum compactum.

Examples of a typical epithelium having a basement membrane include, butare not limited to the following: the epithelium of the skin, intestine,urinary bladder, esophagus, stomach, cornea, and liver. The epithelialbasement membrane may be in the form of a thin sheet of extracellularmaterial contiguous with the basilar aspect of epithelial cells. Sheetsof aggregated epithelial cells of similar type form an epithelium.Epithelial cells and their associated epithelial basement membrane maybe positioned on the lumenal portion of the tunica mucosa and constitutethe internal surface of tubular and hollow organs and tissues of thebody. Connective tissues and the submucosa, for example, are positionedon the abluminal or deep side of the basement membrane. Examples ofconnective tissues used to form the ECMs that are positioned on theabluminal side of the epithelial basement membrane include the submucosaof the intestine and urinary bladder (UBS), and the dermis andsubcutaneous tissues of the skin. The submucosa tissue may have athickness of about 80 micrometers, and consists primarily (greater than98%) of a cellular, eosinophilic staining (H&E stain) extracellularmatrix material. Occasional blood vessels and spindle cells consistentwith fibrocytes may be scattered randomly throughout the tissue.Typically the material is rinsed with saline and optionally stored in afrozen hydrated state until used.

Fluidized UBS, for example, can be prepared in a manner similar to thepreparation of fluidized intestinal submucosa, as described in U.S. Pat.No. 5,275,826 the disclosure of which is expressly incorporated hereinby reference. The UBS is comminuted by tearing, cutting, grinding,shearing or the like. Grinding the UBS in a frozen or freeze-dried stateis preferred although good results can be obtained as well by subjectinga suspension of submucosa pieces to treatment in a high speed (highshear) blender and dewatering, if necessary, by centrifuging anddecanting excess water. Additionally, the comminuted fluidized tissuecan be solubilized by enzymatic digestion of the bladder submucosa witha protease, such as trypsin or pepsin, or other appropriate enzymes fora period of time sufficient to solubilize said tissue and form asubstantially homogeneous solution.

The coating for the stent may be powder forms of UBS. In one embodimenta powder form of UBS is prepared by pulverizing urinary bladdersubmucosa tissue under liquid nitrogen to produce particles ranging insize from 0.1 to 1 mm². The particulate composition is then lyophilizedovernight and sterilized to form a solid substantially anhydrousparticulate composite. Alternatively, a powder form of UBS can be formedfrom fluidized UBS by drying the suspensions or solutions of comminutedUBS.

Other examples of ECM material suitable for use with the presentinvention include but are not limited to fibronectin, fibrin,fibrinogen, collagen, including fibrillar and non-fibrillar collagen,adhesive glycoproteins, proteoglycans, hyaluronan, secreted proteinacidic and rich in cysteine (SPARC), thrombospondins, tenacin, and celladhesion molecules, and matrix metalloproteinase inhibitors.

The stent may be processed in such a way as to adhere an ECM covering(or other material) to only the wire, and not extend between wiresegments or within the stent cells. For instance, one could apply energyin the form of a laser beam, current or heat to the wire stent structurewhile the ECM has been put in contact with the underlying structure.Just as when cooking meat on a hot pan leaves tissue, the ECM could beapplied to the stent in such a manner.

Subsequent to implant of the subject devices, the ECM portion of theimplant is eventually resorbed by the surrounding tissue, taking on thecellular characteristics of the tissue, e.g., endothelium, smoothmuscle, adventicia, into which it has been resorbed. Still yet, an ECMscaffolding having a selected configuration may be operatively attachedto a stent or stent graft of the present invention at a selectedlocation whereby the ECM material undergoes subsequent remodeling tonative tissue structures at the selected location. For example, the ECMscaffolding may be positioned at the annulus of a previously removednatural aortic valve configured in such a way as to create thestructural characteristics of aortic valve leaflets and whereby theimplant provides valve function.

The subject stents, grafts and/or stent grafts may be coated in order toprovide for local delivery of a therapeutic or pharmaceutical agent tothe disease site. Local delivery requires smaller dosages of therapeuticor pharmaceutical agent delivered to a concentrated area; in contrast tosystemic dosages which require multiple administrations and loss ofmaterial before reaching the targeted disease site. Any therapeuticmaterial, composition or drug, may be used including but not limited to,dexamethasone, tocopherol, dexamethasone phosphate, aspirin, heparin,coumadin, urokinase, streptokinase and TPA, or any other suitablethrombolytic substance to prevent thrombosis at the implant site.Further therapeutic and pharmacological agents include but are notlimited to tannic acid mimicking dendrimers used as submucosastabilizing nanomordants to increase resistance to proteolyticdegradation as a means to prevent post-implantational aneurysmdevelopment in decellularized natural vascular scaffolds, cell adhesionpeptides, collagen mimetic peptides, hepatocyte growth factor,proliverative/antimitotic agents, paclitaxel, epidipodophyllotoxins,antibiotics, anthracyclines, mitoxantrone, bleomycins, plicamycin, andmitomycin, enzymes, antiplatelet agents, non-steroidal agents,heteroaryl acetic acids, gold compounds, immunosuppressives, angiogenicagents, nitric oxide donors, antisense oligonucleotides, cell cycleinhibitors, and protease inhibitors.

For purposes of agent delivery, the subject stents, grafts and/or stentgrafts are coated with a primer layer onto a surface. The primer layerformulates a reservoir for containing the therapeutic/pharmaceuticalagent. The overlapping region between the primer layer and activeingredient may be modified to increase the permeability of the primerlayer to the active ingredient. For example, by applying a commonsolvent, the active ingredient and the surface layer mix together andthe active ingredient gets absorbed into the primer layer. In addition,the primer layer may also be treated to produce an uneven or roughenedsurface. This rough area entraps the active ingredient and enhances thediffusion rate of the ingredient when the stent is inserted into thepatient's body. As such, the implant has the ability to diffuse drugs orother agents at a controllable rate. Furthermore, one of skill in theart would understand that the subject invention may provide acombination of multiple coatings, such as the primer layer may bedivided into multiple regions, each containing a different activeingredient.

The subject implants may also be seeded with cells of any type includingstem cells, to promote angiogenesis between the implant and the arterialwalls. Methods have included applying a porous coating to the devicewhich allows tissue growth into the interstices of the implant surface.Other efforts at improving host tissue in growth capability and adhesionof the implant to the host tissue have involved including anelectrically charged or ionic material in the tissue-contacting surfaceof the device.

The stent, graft, or stent graft of the present invention may alsoinclude a sensor or sensors to monitor pressure, flow, velocity,turbidity, and other physiological parameters as well as theconcentration of a chemical species such as for example, glucose levels,pH, sugar, blood oxygen, glucose, moisture, radiation, chemical, ionic,enzymatic, and oxygen. The sensor should be designed to minimize therisk of thrombosis and embolization. Therefore, slowing or stoppage ofblood flow at any point within the lumen must be minimized. The sensormay be directly attached to the outer surface or may be included withina packet or secured within the material of the stent, graft, or stentgraft of the present invention. The biosensor may further employ awireless means to deliver information from the implantation site to aninstrument external to the body.

The stent, graft or stent graft may be made of visualization materialsor be configured to include marking elements, which provide anindication of the orientation of the device to facilitate properalignment of the stent at the implant site. Any suitable materialcapable of imparting radio-opacity may be used, including, but notlimited to, barium sulfate, bismuth trioxide, iodine, iodide, titaniumoxide, zirconium oxide, metals such as gold, platinum, silver, tantalum,niobium, stainless steel, and combinations thereof. The entire stent orany portion thereof may be made of or marked with a radiopaque material,i.e., the crowns of the stent.

It is also contemplated that therapeutic or diagnostic components ordevices may be integrated with the subject implants. Such devices mayinclude but are not limited to prosthetic valves, such as cardiac valves(e.g., an aortic or pulmonary valve) and venous valves, sensors tomeasure flow, pressure, oxygen concentration, glucose concentration,etc., electrical pacing leads, etc. For example, as illustrated in FIG.9, an implant 140 for treating the aortic root is provide which includesa mechanical or biological prosthetic valve 142 employed at a distal endof the main lumen 146. Device 140 further includes two smaller,generally opposing side branch lumens 148 a and 148 b adjustably alignedfor placement within the right and left coronary ostia, respectively.The length of the stent graft may be selected to extend to a selecteddistance where it terminates at any location prior to, within orsubsequent to the aortic arch, e.g., it may extend into the descendingaorta. Any number of additional side branches may be provided foraccommodating the aortic arch branch vessels.

Those skilled in the art will appreciate that any suitable stent orgraft configuration may be provided to treat other applications at othervascular locations at or near the intersection of two or more vessels(e.g., bifurcated, trifurcated, quadrificated, etc.) including, but notlimited to, the aorto-illiac junction, the femoral-popiteal junction,the brachycephalic arteries, the posterior spinal arteries, coronarybifurcations, the carotid arteries, the superior and inferior mesentericarteries, general bowel and stomach arteries, cranial arteries andneurovascular bifurcations.

The devices of the present invention are deliverable throughendovascular or catheter-based approaches whereby the device ispositioned within a delivery system in a reduced shape and size andcaused to expand to an expanded shape and dimension upon deployment fromthe system. The devices may be designed to be self-expanding uponrelease from a delivery system, i.e., catheter or sheath, or may requireactive expansion by separate means, such as a balloon or otherexpandable or inflatable devices. Still yet, other devices may bedeployable with a combination of a passive and active deployment system.Any suitable stent delivery technique may be employed to deliver thestents, grafts and stent grafts of the present invention, where thoseskilled in the art will recognize certain features that may be made tothe stent, graft or stent graft to accommodate a particular deploymentmethod.

For example, self-expanding devices of the present invention aretypically fabricated from materials that may be superelastic materials,such as nickel-titanium alloys, spring steel, and polymeric materials.Alternatively or additionally, the particular weave pattern used to formthe cells of the device incorporates a radial spring force thatself-expands upon release from a delivery system.

If more control is desired in deployment of self-expanding devices, thedevices may be configured for delivery and deployment by use of one ormore designated deployment members, including but not limited to lines,strings, filaments, fibers, wires, stranded cables, tubings, etc. Thedeployment members are releasably attached to the device, such as bybeing looped through one or more apices of the device, and used toretain the device in a constrained condition as well as to release thedevice from the constrained condition. More particularly, the deploymentmembers may be selectively tensioned, pulled and/or released to releasethe apices and deploy the device. Examples of such stent deliverysystems are disclosed in U.S. Pat. No. 6,099,548, U.S. PatentPublication Nos. 2006/0129224 and 2006/0155366, and co-pending U.S.patent application Ser. No. 11/539,478 filed Oct. 6, 2006 and U.S.Patent Applications having U.S. Pat. No. 12/029,180 filedcontemporaneously herewith, both entitled Apparatus and Method forDeploying an Implantable Device Within the Body and incorporated hereinby reference.

Other means of releasable attachment which may be employed with thedelivery systems to deploy the subject devices include but are notlimited to electrolytic erosion, thermal energy, magnetic means,chemical means, mechanical means or any other controllable detachmentmeans.

In some applications, active deployment systems including expandableballoons and the like may also be used to deploy the stents of thepresent invention. Examples of balloon expandable stent delivery systemsare disclosed in U.S. Pat. Nos. 6,942,640, 7,056,323, 7,070,613 and7,105,014.

It is also contemplated that the implantable devices may be delivered byuse of a delivery system that enables partial deployment of the deviceprior to full deployment in order to facilitate proper placement of thedevice. Additionally, the selected delivery system may provide for theindividual and independent deployment of each lumenal end of theimplantable devices, where some or all of the lumenal ends may besimultaneously deployed or serially deployed in an order that bestfacilitates the implantation procedure.

The preceding merely illustrates the principles of the invention. Itwill be appreciated that those skilled in the art will be able to devisevarious arrangements which, although not explicitly described or shownherein, embody the principles of the invention and are included withinits spirit and scope. Furthermore, all examples and conditional languagerecited herein are principally intended to aid the reader inunderstanding the principles of the invention and the conceptscontributed by the inventors to furthering the art, and are to beconstrued as being without limitation to such specifically recitedexamples and conditions. Moreover, all statements herein recitingprinciples, aspects, and embodiments of the invention as well asspecific examples thereof, are intended to encompass both structural andfunctional equivalents thereof. Additionally, it is intended that suchequivalents include both currently known equivalents and equivalentsdeveloped in the future, i.e., any elements developed that perform thesame function, regardless of structure. The scope of the presentinvention, therefore, is not intended to be limited to the exemplaryembodiments shown and described herein. Rather, the scope and spirit ofpresent invention is embodied by the appended claims.

It must be noted that as used herein and in the appended claims, thesingular forms “a”, “an”, and “the” include plural referents unless thecontext clearly dictates otherwise. Thus, for example, reference to “awire” may include a plurality of such wires and reference to “the stentlumen” includes reference to one or more stent lumens and equivalentsthereof known to those skilled in the art, and so forth.

Where a range of values is provided, it is understood that eachintervening value, to the tenth of the unit of the lower limit unlessthe context clearly dictates otherwise, between the upper and lowerlimits of that range is also specifically disclosed. Each smaller rangebetween any stated value or intervening value in a stated range and anyother stated or intervening value in that stated range is encompassedwithin the invention. The upper and lower limits of these smaller rangesmay independently be included or excluded in the range, and each rangewhere either, neither or both limits are included in the smaller rangesis also encompassed within the invention, subject to any specificallyexcluded limit in the stated range. Where the stated range includes oneor both of the limits, ranges excluding either or both of those includedlimits are also included in the invention.

All publications mentioned herein are incorporated herein by referenceto disclose and describe the methods and/or materials in connection withwhich the publications are cited. The publications discussed herein areprovided solely for their disclosure prior to the filing date of thepresent application. Nothing herein is to be construed as an admissionthat the present invention is not entitled to antedate such publicationby virtue of prior invention. Further, the dates of publication providedmay be different from the actual publication dates which may need to beindependently confirmed.

That which is claimed is:
 1. An implantable stent for use in a vessel ortubular structure comprising: a unitary structure having a main lumenformed of struts and at least one side branch lumen formed of struts,wherein the main lumen has a main lumen first end and a main lumensecond end, wherein the at least one side branch lumen has a side branchlumen first end and a side branch lumen second end, wherein the strutsforming the side branch lumen first end are connected to the strutsforming the main lumen between the main lumen first end and the mainlumen second end, wherein the main lumen and the side branch lumen havea pattern of interconnected cells, wherein the size of theinterconnected cells of the side branch lumen varies along a distallength of the side branch lumen, wherein an angle between the at leastone side branch lumen and the main lumen is adjustable between a firstangle and a second angle, wherein when the angle is the first angle, theside branch lumen second end is closer to the main lumen first end thanto the main lumen second end, and wherein when the angle is the secondangle, the side branch lumen second end is closer to the main lumensecond end than to the main lumen first end.
 2. The implantable stent ofclaim 1, wherein the unitary structure comprises one or more sectionshaving cells having a first size and one or more other sections havingcells having a second size different from the first size.
 3. Theimplantable stent of claim 1, wherein the main lumen has at least onesection of smaller cells adjacent at least one side branch lumen.
 4. Theimplantable stent of claim 1, wherein the struts comprise first strutsand second struts, wherein the first struts are thicker than the secondstruts, and wherein the first and second struts extend along a length ofthe main branch lumen.
 5. The implantable stent of claim 1, wherein athickness of a strut forming one of the cells at a first or second endof the main lumen is greater than a thickness of a strut forming anothercell at another portion of the main lumen.
 6. The implantable stent ofclaim 1, further comprising a graft material, wherein the graft materialis adjacent at least a portion of the main lumen and at least a portionof the at least one side branch lumen, and wherein the graft materialhas ridges and grooves.
 7. The implantable stent of claim 1, wherein thesize of the interconnected cells of the side branch lumen decreasesalong the distal length of the side branch lumen.
 8. The implantablestent of claim 1, wherein the size of the interconnected cells of theside branch lumen progressively decreases from the side branch lumenfirst end to the side branch lumen second end.
 9. An implantable stentfor use in a vessel or tubular structure comprising: interconnectedcells forming a main lumen and at least one side branch lumen, whereinthe main lumen has a main lumen first end and a main lumen second end,wherein the at least one side branch lumen has a side branch lumen firstend and a side branch lumen second end, wherein the side branch lumenfirst end is connected to the main lumen, wherein when the at least oneside branch lumen is in a fully deployed configuration, the at least oneside branch lumen is between the main lumen first end and the main lumensecond end, wherein an angle between the at least one side branch lumenand the main lumen is adjustable between a first angle and a secondangle, wherein when the angle is the first angle and the at least oneside branch lumen is in the fully deployed configuration, the sidebranch lumen second end is closer to the main lumen first end than tothe main lumen second end, wherein the stent has one or more sectionshaving cells having a first size and one or more other sections havingcells having a second size different from the first size, and whereinthe size of the cells of the main branch lumen progressively decreasesfrom a main branch lumen medial portion to at least one of the mainbranch lumen first end and the main branch lumen second end.
 10. Theimplantable stent of claim 9, wherein the main lumen has at least onesection of smaller cells relative to cells of at least one side branchlumen, wherein the at least one side branch lumen comprises two sidebranch lumens, and wherein at least a portion of the at least onesection of smaller cells is between the two side branch lumens.
 11. Theimplantable stent of claim 9, wherein when the at least one side branchlumen is in the fully deployed configuration, the cell size of the atleast one side branch lumen is progressively reduced in the distaldirection from the side branch lumen first end to the side branch lumensecond end such that the cell size is smaller at the side branch lumensecond end than at the side branch lumen first end.
 12. The implantablestent of claim 9, wherein a first or second end of the main lumen hasstruts with a thickness greater than struts of another portion of themain lumen; and/or wherein the stent is configured to be attached to asensor or a valve.
 13. The implantable stent of claim 9, furthercomprising a graft material, wherein the graft material is adjacent atleast a portion of the main lumen and at least a portion of the at leastone side branch lumen, and wherein the graft material has ridges andgrooves wherein when the angle is the second angle and the at least oneside branch lumen is in the fully deployed configuration, the sidebranch lumen second end is closer to the main lumen second end than tothe main lumen first end.
 14. The implantable stent of claim 9, furthercomprising a graft material, wherein the graft material is adjacent atleast a portion of the main lumen and at least a portion of the at leastone side branch lumen, and wherein the graft material has ridges andgrooves, wherein the ridges and grooves extend within or around at leasta portion of a circumference of the main lumen and at least one of theat least one side branch lumen, and wherein the ridges and groovesextend in a longitudinal direction along at least one of the main lumenand at least one of the at least one side branch lumen.
 15. Animplantable stent for use in a vessel or tubular structure comprising:interconnected struts forming a main lumen and at least one side branchlumen, wherein the main lumen has a main lumen first end and a mainlumen second end, wherein the at least one side branch lumen has a sidebranch lumen first end and a side branch lumen second end, wherein theside branch lumen first end is attached to the main lumen, wherein whenthe at least one side branch lumen is in a fully deployed configuration,the side branch lumen second end is between the main lumen first end andthe main lumen second end, wherein an angle between the at least oneside branch lumen and the main lumen is adjustable such that the atleast one side branch lumen is adjustable between a first configurationand a second configuration, wherein when the at least one side branchlumen is in the first configuration and the at least one side branchlumen is in the fully deployed configuration, the side branch lumensecond end is closer to the main lumen first end than to the main lumensecond end, wherein the main lumen has cells having a first size,wherein at least one side branch lumen has cells having a second sizedifferent from the first size, wherein the at least one side branchlumen has a first distal section of cells and a second distal section ofcells, wherein the size of the cells of the first distal section islarger than the size of the cells of the second distal section, andwherein the second distal section is closer to the side branch lumensecond end than the first distal section.
 16. The implantable stent ofclaim 15, wherein the main lumen has at least one section of smallercells adjacent at least one side branch lumen wherein when the at leastone side branch lumen is in the second configuration and the at leastone side branch lumen is in the fully deployed configuration, the sidebranch lumen second end is closer to the main lumen second end than tothe main lumen first end.
 17. The implantable stent of claim 15, whereinthe main lumen has at least one section of smaller cells adjacent atleast one side branch lumen, wherein the cell size of the at least oneside branch lumens gets smaller in the distal direction, and wherein thestent comprises stainless steel, elgiloy, tungsten, platinum, orNITINOL.
 18. The implantable stent of claim 15, further comprising agraft material, wherein the graft material is adjacent at least aportion of the main lumen and at least a portion of the at least oneside branch lumen, wherein the graft material has ridges and grooves,and wherein the ridges and grooves extend within or around at least aportion of a circumference of the main lumen and at least one of the atleast one side branch lumen.
 19. The implantable stent of claim 15,wherein a first or second end of the main lumen has a first strut havinga thickness greater than a second strut at another portion of the mainlumen; and/or wherein the stent is configured to be attached to a sensoror a valve.
 20. The implantable stent of claim 15, wherein the size ofthe cells of the side branch lumen progressively decreases from the sidebranch lumen first end to the side branch lumen second end.